Etravirine dose selection in children aged 6 to 17
Polly Clayden, HIV i-Base
Chistoph Konigs and coworkers from paediatric centres in Europe performed a dose finding study of etravirine (ETR) in treatment experienced children >6 years and weighing >20kg.
This was a phase 1, open label trial in two sequential stages. 21 HIV-positive children on stable lopinavir/r-based ART with viral load <50 copies/mL were enrolled in each stage. Children in stage I received 4mg/kg ETR bid following a meal (included in HTB reports from CROI last year). Children in Stage II received 5.2mg/kg ETR bid following a meal. ETR was added to background regimen for 7 days. After the morning dose on day 8 the investigators performed a 12 hour PK evaluation. 100mg and proportional 25mg tablets were used in this study. PK for 19 and 20 children were available in stages I and II, respectively.
The investigators reported the mean (SD) Cmax in stage I and II, respectively, was 495 (453) and 757 (680) ng/mL; Cmin was 184 (151) and 294 (278) ng/mL; and AUC12h was 4050 (3602) and 6141 (5586) ngh/mL.
When they compared PK parameters to those reported in adult trials (n = 575), population derived Cmin was 393  ng/mL and AUC12h was 5506  ngh/mL, they found the levels achieved in children participating in stage II with the higher dose to be more appropriate.
All children had a viral load <50 copies/mL on day 8. The majority of side effects were grade 1 or 2, most commonly rhinitis or headache. Two children in stage 1 had a mild to moderate rash on day 8. No child discontinued treatment due to toxicity.
The target dose of ETR in children 6-17 years was selected as 5.2mg/kg bid, which provides comparable exposure to the adult dose of 200mg bid.
Further studies in children are ongoing or planned.
Tibotec intend to market the 25-mg tablet for children (and adults who have difficulty swallowing the 100-mg tablets) once they have the initial paediatric indication.
Konigs et al. Pharmacokinetics and dose selection of etravirine in HIV-infected children between 6 and 17 years inclusive. 16th CROI, February 2009, Montreal, Canada. Poster abstract 879.